Project Summary Images play important roles in interventional procedures that aims at changing tissue perfusion or blood flow such as endovascular mechanical thrombectomy for acute ischemic stroke and trans-arterial chemo- embolization and selective internal radiation therapy using yittrium-90 microspheres for liver tumor oncology. One of the problems is that soft tissue perfusion cannot be assessed in an interventional suite. If tissue perfusion could be assessed in real-time, prior to, during, or just after a core procedure is performed, it would allow for targeting a lesion more precisely, minimizing the side effect, assessing the change of perfusion quantitatively immediately after the procedure is completed, and performing an additional procedure if necessary. These are unmet clinical needs we plan to address in this project. We propose to develop a time-resolved Intra-operative four-dimensional soft tissue PErfusion method using No gantry rotation (IPEN). IPEN is expected to achieve a sub-second temporal resolution (<0.3 sec/image), a large field-of-view (30?40 cm), a radiation dose comparable to one series of angiogram, and a smooth workflow; IPEN uses a single- or bi-plane, standard C-arm flat-panel x-ray system, and thus, requires no additional equipment cost. The innovation with IPEN is not to reconstruct volumetric images, because that is the source of problems with CBCT-based perfusion. Instead, IPEN estimates time-enhancement curves (TECs) of multiple regions-of-interest (ROIs) directly from X-ray ProjEctions acquired with No gantry rotation, which we call ?XPEN images.? Contours of ROIs will be obtained from a pre-operative MDCT and ROIs include arteries, veins, sub-lesions of cancers, infarct and penumbra, and parenchyma directly next to the targeted area. In this project, we will develop the IPEN algorithm and assess it using a realistic computer simulation study in Specific Aim 1 and then validate it using an animal study in Specific Aim 2. The success will be measured by the accuracy of TECs and perfusion indices in both of the studies. The success will be measured by the accuracy of TECs and perfusion indices computed from TECs in both of the studies. By the end of 2 years, we will have the IPEN algorithm developed and validated thoroughly using simulations and animal studies. We will then plan an R01 study with patient data.